Therapeutic approaches that reprogram the gut microbiome are promising strategies to alleviate and cure inflammatory bowel disease (IBD). However, abnormal expansion of Escherichia coli during inflammation can promote pathogenic bacteria occupying ecological niches to resist reprogramming of the microbiome. Herein, a bionic regulator (CaWO₄@YCW) is developed to efficiently and precisely regulate the gut microbiome by specifically suppressing the abnormal expansion of E. coli during colitis and boosting probiotic growth. Inspired by the binding of E. coli strains to the mannose-rich yeast cell wall (YCW), YCW is chosen as the bionic shell to encapsulate CaWO₄. It is demonstrated that the YCW shell endows CaWO₄ with superior resistance to the harsh environment of the gastrointestinal tract and adheres to the abnormally expanded E. coli in colitis, specifically as a positioner. Notably, the high expression of calprotectin at the colitis site triggers the release of tungsten ions through calcium deprivation in CaWO₄, thus inhibiting E. coli growth by replacing molybdenum in the molybdopterin cofactor. Moreover, YCW functions as a prebiotic and promotes probiotic growth. Consequently, CaWO₄@YCW can efficiently and precisely reprogram the gut microbiome by eliminating pathogenic bacteria and providing prebiotics, resulting in an extraordinary therapeutic advantage for DSS-induced colitis.

中文翻译：

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仿生调节剂打破了病原菌的生态位，用于调节结肠炎中失调的微生物组

重新编程肠道微生物组的治疗方法是缓解和治愈炎症性肠病 (IBD) 的有希望的策略。然而，大肠杆菌在炎症过程中的异常扩张可以促进病原菌占据生态位以抵抗微生物组的重编程。在此，我们开发了一种仿生调节剂 (CaWO ₄ @YCW)，通过特异性抑制结肠炎期间大肠杆菌的异常扩张和促进益生菌的生长，有效、精确地调节肠道微生物组。受大肠杆菌菌株与富含甘露糖的酵母细胞壁 (YCW) 结合的启发，选择 YCW 作为包裹 CaWO ₄的仿生壳。证明了 YCW 壳赋予 CaWO₄对胃肠道的恶劣环境具有超强的抵抗力，并粘附在结肠炎中异常膨胀的大肠杆菌上，特别是作为定位器。值得注意的是，结肠炎部位钙卫蛋白的高表达通过CaWO ₄中的钙剥夺触发钨离子的释放，从而通过取代钼蝶呤辅因子中的钼来抑制大肠杆菌的生长。此外，YCW 作为益生元发挥作用并促进益生菌生长。因此，CaWO ₄ @YCW 可以通过消除病原菌和提供益生元来有效和精确地重新编程肠道微生物组，从而为 DSS 诱导的结肠炎带来非凡的治疗优势。